With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.502649-32-3,1-Boc-3-Isopropylpiperazine,as a common compound, the synthetic route is as follows.
Exchanging 2,4-dichloropyrimidine for 2,4-dichloro-5-fluoropyrimidine and phenylboronic acid for 2-(4-(methoxymethyl)phenyl)-4,4,5,5-tetramethyl-l,3,2- dioxaborolane, the first step of Example 137 was used to prepare 2-chloro-5-fluoro-4-(4- (methoxymethyl)phenyl)pyrimidine. To a stirred solution of this intermediate (0.400 g, 1.58 mol) in toluene (8 mL) was added tert-butyl 3-isopropylpiperazine-l-carboxylate (0.434 g, 1.90 mmol), bis(tri-tert-butylphosphine)palladium(0) (0.081 g, 0.158 mmol), trimethylhexadecylammonium chloride (0.101 g, 0.316 mmol) and a 50% aqueous sodium hydroxide solution (0.25 mL, 4.73 mmol). The mixture was heated at 100 C overnight and concentrated. The residue was purified by flash chromatography over silica using a hexane/ethyl acetate eluant to afford partially purified tert-butyl 4-(5-fluoro-4-(4- (methoxymethyl)phenyl)pyrimidin-2-yl)-3 -isopropylpiperazine- 1 -carboxylate as light yellow oil (0.500 g). This material was taken up in dichloromethane (5 mL), stirred and treated with trifluoroacetic acid (3.0 mL). After 3 hours, the reaction was concentrated and the residue was purified by reversed-phase flash chromatography over CI 8 silica using a acetonitrile/water/trifluoroacetic acid eluant. 5-Fluoro-2-(2-isopropylpiperazin-l- yl)-4-(4-(methoxymethyl)phenyl)pyrimidine was afforded as a light yellow oil (0.200 g, 36% for two steps). Using General Procedure A and Intermediate 5, this intermediate was used to generate the title compound as a white solid (0.105 g, 63%). 1H NMR (500 MHz, CDCls) delta 8.24 (d, J = 3.5 Hz, 1H), 8.08 (d, J = 8.0 Hz, 2H), 7.48 (d, J = 8.5 Hz, 2H), 4.75-4.72 (m, 1H), 4.59-4.55 (m, 3H), 4.33-4.31 (m, 1H), 3.94-3.86 (m, 2H), 3.45 (s, 3H), 3.28-3.19 (m, 2H), 3.07-2.85 (m, 7H), 2.43-2.40 (m, 1H), 2.26-2.19 (m, 1H), 1.94-1.50 (m, 9H), 1.13 (t, J = 7.5 Hz, 3H), 0.87 (d, J = 7.5 Hz, 3H) ppm. 13C NMR (125 MHz, CDCI3) delta 158.4, 157.0, 151.1, 151.0, 150.4, 148.4, 146.7, 146.4, 140.9, 133.4, 129.0, 128.9, 127.5, 74.2, 59.0, 58.3, 57.5, 57.3, 53.2, 47.8, 47.6, 46.4, 46.1, 44.0, 43.9, 43.5, 43.3, 39.9, 39.7, 39.1, 36.7, 36.4, 27.1, 27.0, 25.9, 25.7, 24.4, 24.1, 20.4, 20.2, 19.1, 19.0 ppm. Purity: > 99% LCMS (214 nm & 254 nm); retention time 1.54 min; (M+H+) 525.3., 502649-32-3
As the paragraph descriping shows that 502649-32-3 is playing an increasingly important role.
Reference£º
Patent; GENZYME CORPORATION; BOURQUE, Elyse; CABRERA-SALAZAR, Mario, A.; CELATKA, Cassandra; CHENG, Seng, H.; HIRTH, Bradford; GOOD, Andrew; JANCSICS, Katherine; MARSHALL, John; METZ, Markus; SCHEULE, Ronald, K.; SKERLJ, Renato; XIANG, Yibin; ZHAO, Zhong; LEONARD, John; NATOLI, Thomas; MAKINO, Elina; HUSSON, Herve; BESKROVNAYA, Oxana; WO2014/43068; (2014); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics